Pratt C B, Stewart C, Santana V M, Bowman L, Furman W, Ochs J, Marina N, Kuttesch J F, Heideman R, Sandlund J T
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.
J Clin Oncol. 1994 Mar;12(3):539-43. doi: 10.1200/JCO.1994.12.3.539.
To determine the dose-limiting toxicity and potential efficacy of topotecan in pediatric patients with refractory malignant solid tumors.
In this phase I clinical trial, 27 patients received topotecan 0.75-1.9 mg/m2 by continuous intravenous infusion daily for 3 days. Fifty-three treatment courses were given to these patients.
Myelosuppression was the dose-limiting toxicity at levels of 1.3 to 1.9 mg/m2 for 3 days, requiring significant support with transfused packed RBCs and platelets. Myelosuppression was variable in severity at the 1.0-mg/m2 dosage level; thus, additional patients were treated with this dosage, followed by human recombinant granulocyte-colony stimulating factor (G-CSF). Other toxicities were not significant. One patient with neuroblastoma had a complete response that lasted for 8 months. Stable disease activity was recorded for other patients with neuroblastoma, rhabdomyosarcoma, and islet cell carcinoma. Pharmacokinetic studies showed that topotecan plasma concentrations ranged from 1.6 to 7.5 ng/mL during infusions of 1.0 mg/m2/d, and that there was a biphasic plasma distribution with a mean terminal half-life of 2.9 +2- 1.0 hours.
Topotecan is a promising anticancer agent that deserves phase II testing in pediatric solid tumors. We recommend that pediatric phase II topotecan trials use 1.0 mg/m2/d for 3 days as a constant intravenous infusion, followed by G-CSF for 14 days, and that these treatment courses be repeated every 21 days.
确定拓扑替康对难治性恶性实体瘤患儿的剂量限制性毒性和潜在疗效。
在这项I期临床试验中，27例患者每日接受拓扑替康0.75 - 1.9 mg/m²持续静脉输注，共3天。这些患者共接受了53个疗程的治疗。
骨髓抑制是剂量限制性毒性，在1.3至1.9 mg/m²剂量水平持续3天时出现，需要输注红细胞和血小板进行显著支持。在1.0 mg/m²剂量水平，骨髓抑制的严重程度不一；因此，更多患者接受了该剂量治疗，随后使用人重组粒细胞集落刺激因子（G-CSF）。其他毒性不显著。1例神经母细胞瘤患者出现完全缓解，持续8个月。其他神经母细胞瘤、横纹肌肉瘤和胰岛细胞癌患者记录为疾病稳定。药代动力学研究表明，在1.0 mg/m²/d输注期间，拓扑替康血浆浓度范围为1.6至7.5 ng/mL，血浆分布呈双相性，平均终末半衰期为2.9±1.0小时。
拓扑替康是一种有前景的抗癌药物，值得在儿童实体瘤中进行II期试验。我们建议儿童II期拓扑替康试验采用1.0 mg/m²/d持续静脉输注3天，随后使用G-CSF 14天，且每21天重复这些疗程。
